Prevention and improvement of allergy caused by leucotriene B 4

ABSTRACT

A composition such as foods, drinks, pharmaceutical composition, for prevention or improvement of allergy, comprising an omega 9 series unsaturated fatty acid such as 6,9-octadecadienoic acid, 8,11-eicosadienoic acid, 5,8,11-eicosatrienoic acid etc.

This application is a continuation of application Ser. No. 08/249,996,filed May 27, 1994, now abandoned.

BACKGROUND OF INVENTION

1. Field of Invention

The present invention relates to a composition for prevention orimprovement of medical symptoms caused by leucotriene B4 (LTB₄),comprising as an effective ingredient an omega 9 series unsaturatedfatty acid. More specifically, the present invention relates acomposition for prevention or improvement of inflammation, especiallychronic inflammation such as rheumatoid arthritis, or allergy,comprising at least one effective ingredient selected from the groupconsisting of 6,9-octadecadienoic acid, 8,11-eicosadienoic acid and5,8,11-eicosatrienoic acid.

2. Related Art

Inflammation is a defence reaction of organisms caused by a physical orchemical stimulation, immunological phenomena involving antibodies,immune complex, degradation products of complements, or the like. Duringthe inflammation, characteristic phenomena occur including expansion andperforation of microvessels, leak of blood components into spacesbetween tissues, migration of leucocytes to an inflammatory tissue, andthe like, resulting in symptoms such as erythema, edema, hyperalgesia,ache etc. In a process of inflammation, various pharmacologically activesubstances are locally formed and liberated, and mediate inflammatoryreactions. These substances are called chemical mediators ofinflammation, and include plasmakinins such as bradykinin, serotonin,histamines and the like, prostaglandin (PG), leucotriene (LT), variousleucocyte migration enhancement factors, and the like.

Allergy is a condition wherein reaction harmful to an organism, such asdestruction and abnormal reaction of tissue results from an immuneresponse. In the allergy process, it is known that an allergen invadesan organism and reacts with IgE antibody fixed to mast cell orbasophilic leukocyte resulting in liberation of a chemical transmittersuch as histamines, leucotriene (LT), eosinophilic migration enhancementfactor, neutrophilic migration enhancement factor, and the like,providing cell infiltration, destruction of tissues, contraction ofsmooth muscle, stimulation of vascular permeability, stimulation ofmucous secretion etc.

Generally, although anti-inflammatory drugs are used for inhibitinginflammatory symptoms and alleviating destruction of tissues, in thebroad sense, they include allergic reaction inhibitory drugs(anti-allergic drugs). Currently available anti-inflammatory drugs areclassified as steroidal anti-inflammatory drugs (adrenocorticalhormones) and non-steroidal anti-inflammatory drugs. Although thesteroidal anti-inflammatory drugs provide strong anti-inflammatoryaction, they also exhibit strong side-effects, and thereforedetermination of termination of and method for administration isdifficult. On the other hand, although acidic non-steroidalanti-inflammatory drugs such as aspirin, indomethacin etc. exhibitanti-inflammatory action by lowering cycloxygenase activity andinhibiting PG synthesis, and are used as frequently as antibiotics andlanking after steroidal drugs, they provide side effects such asgastrointestinal injurys, nephrotoxicity, hemopoietic disorders, andtherefore their use is very limited.

A more recent approach to the moderation of inflammatory andhypersensitivity responses has focused on blocking the action ofarachidonic acid metabolites (including the prostaglandins),lipoxygenases and the leukotrienes. The leukotrienes (LT) metabolitesare formed by oxygenation of a lipoxygenase (5-hydroperoxytetraenoicacid (5-HPETE)) which is formed by the specific oxygenation of the C-5position of arachidonic acid. The first leukotriene formed in themetabolic pathway is the unstable epoxide intermediate leukotriene A₄(LTA₄) which is the precursor to the family of peptide-leukotrienes, thefirst in the pathway being LTC₄ which is formed by glutathione addition.LTC₄ is transformed subsequently into LTD₄ and LTE₄ by successiveelimination of a glutamyl and glycine residue. The peptido-leukotrienesprimarily act on smooth muscle and other cells having contractilecapacity, as well as playing a key role in hypersensitivity reactions.In addition, the peptido-leukotrienes are spasmogens, increase vascularpermeability, activate airway smooth muscle, stimulate mucous secretionand are involved with the pathogenesis of certain inflammatory diseasessuch as bronchitis, ectopic and atopic eczema and psoriasis.Leukotrienes appear to be involved in the pathogenesis of asthma such asallergic pulmonary disorders of asthma, hay fever and allergic rhinitis.In addition, LTC₄, LTD₄ and LTE₄ may also decrease blood pressure by anaction on the heart, because they reduce myocardial contractility andcoronary blood flow.

Another family of leukotrienes, the LTB₄, is derived from LTA₄ byhydrolase-catalyzed addition of water. This 5,12-dihydroxy derivative,causes adhesion and chemotactic movement of leukocytes, stimulatesaggregation, enzyme release and generation of superoxide in neutrophils.Additionally, LTB₄ is a potent chemotactic and chemokinetic agent foreosinophils, macrophages and monocytes, stimulates suppressor Tlymphocytes and enhances natural cytotoxic cell activity. LTB₄ is also apotent (indirect) bronchoconstrictor but in contrast to thepeptido-leukotrienes C₄, D₄ and E₄ does not appreciably stimulate mucousproduction and induce edema of the airways by increasing vascularpermeability.

It has been suggested that compounds antagonizing LTB₄ activity may bevaluable in the treatment of inflammatory diseases caused by tissuedegrading enzymes and reactive chemicals liberated bytissue-infiltrating and aggregating polymorphonuclear leukocytes.

For example, PCT Japanese National Publication No. 6-502164 describesthat novel monocyclic or bicyclic aryl compounds are selectivelyantagonistic to LTB₄ and are useful for treatment of rheumatoidarthritis, gout, psoriasis and inflammatory bowel disease. JapaneseUnexamined Patent Publication (Kokai) No. 4-244023 describes that ω6series unsaturated fatty acids such as dihome-γ-linolenic acid areuseful for treatment of arrhythmia, acute myocardial infarction etc. byinhibiting production of LTB₄. Japanese Unexamined Patent PublicationNo. 5-310668 describes that a novel leucine derivative has an inhibitoryaction to LTA₄ hydrolase and are useful for treatment and prophylaxis ofallergic diseases such as bronchial asthma, various inflammatorydiseases, ischemia-reperfusion disorders. Japanese Unexamined PatentPublication (Kokai) No. 1-190656 discloses that novel leucotriene B₃dimethyl amide has an antagonistic action to LTB₄ and is useful asanti-inflammatory drug, anti-rheumatic drug and gout-treatment drug.

On the other hand, it is known that 8,11-cis-eicosadienoic acid and5,8,11-cis-eicosatrienoic acid (mead acid), which are omega 9 seriesfatty acids, are produced in animal tissues deficient in essential fattyacids. J. Biolog Chem. Vol. 259, No. 19, pp.11784-11789 (1984) disclosesthat in neutrophile of rat fed on essential fatty acid deficient feed,mead acid was detected, which was not detected in rat fed on normalfeed, and an amount of LTB₄ decreased. However, this phenomenon is undera specific condition of essential fatty acid deficiency, and it is notclear whether mead acid alone inhibits the production of LTB₄ andexhibits anti-inflammatory or anti-allergic action.

In addition, Japanese Unexamined Patent Publication No. 62-129241describes that a particular ester or amide of 5,8,11-eicosatriynoic acidinhibits the metabolism of arachidonic acid caused by cyclooxygenase andlypoxygenase. U.S. Pat. No. 4,432,906 describes that10,10-dimethyl-5,8,11-eicosatrienoic acid and10-methyl-5,8,11-eicosatrienoic acid are useful as anti-allergic drugand anti-asthma drug because they do not inhibit the synthesis of PG,but inhibit the synthesis of SRS-A. U.S. Pat. No. 4,434,101 describesthat 7,7-dimethyl-5,8-eicosadienoic acid and 7-methyl-5,8-eicosadienoicacid are useful as anti-allergic agent and anti-asthma drug because theydo not inhibit the synthesis of PG and inhibit the synthesis of SRS-A.However, it is not clear whether or not omega 9 series unsaturated fattyacid such as mead acid has LTB₄ production inhibitory action and isuseful as prophylactic or improving drugs for inflammation, especiallychronic inflammation such as rheumatoid arthritis, and allergy.

Arthritic rheumatism a chronic polyinflammatory disease, and in theserum and synovial fluid of rheumatoid arthritis patients rheumatoidfactor which is an autoantibody reactive with immunoglobulin IgG isdetected. Because of the presence of the rheumatoid factor, it isconsidered that the rheumatoid arthritis involves immune disorder.However, the cause of the disease is not known. In the treatment ofrheumatoid arthritis, non-steroidal anti-inflammatory drugs are used forsymptomatic therapy through the entire disease process.

SUMMARY OF THE INVENTION

The present invention provides a pharmaceutical composition effective asa prophylactic or improving drug for medical symptoms caused by LTB₄,especially anti-inflammatory drugs and anti-allergic drugs, and whichexhibits relatively low side effects and is applicable to chronicsymptoms.

The present inventors carried out researches on various unsaturatedfatty acids to accomplish the above-mentioned object, and found omega 9series unsaturated fatty acids which have high LTB₄ -productioninhibitory action and are highly useful for prophylaxis and improvementof medical symptoms caused by LTB₄, and completed the present invention.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 shows an effect of mead acid in a collugen-induced arthritismead.

DETAILED DESCRIPTION OF THE INVENTION

An effective ingredient of the present composition, omega 9 seriesunsaturated fatty acid is a fatty acid wherein the double bond nearestto the methyl terminus of the fatty acid molecule located between theninth carbon atom and the tenth carbon atom calculating from theterminal methyl group, having at least two double hands and preferablyhaving 18 to 22 carbon atoms, and is for example, 6,9-octadecadienoicacid, 8,11-eicosadienoic acid, 5,8,10-eicosatrienoic acid etc. Thesefatty acids can be used alone or in combination. Since all of thenaturally occurring omega 9 series unsaturated fatty acids are cis-type,in the present invention cis-type omega 9 series unsaturated fatty acidsare preferably used. According to the present invention, the omega 9series unsaturated fatty acids can be used not only in a form of a freefatty acid, but also in a form of salts, for example, salts of alkalinemetal such as sodium, potassium, lithium or other alkaline metal, saltsof other metals such as alkaline earth metal, such as zinc, calcium ormagnesium, and in a form of mono-, di- or tri-glyceride, esters of loweralcohols, phospholipid, glycolipid, or amides, and especially ethylester and triglycerides are preferred. Here, the lower alcohol meansmonohydric alcohol having up to 6 carbon atoms, such as methanol,ethanol, propanol, isopropanol, butanol, pentanol, hexanol etc.

Any source of omega 9 series unsaturated fatty acids used can be usedfor the present invention. For example, a fatty acid can be obtained bymicroorganisms capable of producing an omega 9 series unsaturated fattyacid, animal tissues deficient in essential fatty acids, or cultureanimal cells deficient in essential fatty acids, or produced bychemosynthesis or enzymatic synthesis, or extracted and isolated fromanimal cartilage can be used. Particular microorganisms capable ofproducing an omega 9 series unsaturated fatty acid are, for example,microorganisms which have Δ5 desaturase activity and Δ6 desaturaseactivity and having reduced or lost Δ12 desaturase activity, such asMortiellela alpina SAM 1861 (FERM BT-3590), as described in JapaneseUnexamined Patent Publication No. 5-91888.

To extract and isolate free omega 9 series unsaturated fatty acids oresters thereof from the microorganisms, according to a conventionalprocedure, fat and oil extracted with an organic solvent such asn-hexane or supercritical carbon dioxide from the cultured microbialcells, and the fat and oil is subjected to hydrolysis and esterificationto obtain a mixture of fatty acids or a mixture of fatty acid esters,and a desired 6,9-cis-octadecubienoic acid, 8-11-cis-eicosadienoic acid,5,8,11-cis-eicosatrienoic acid etc. in a form of free fatty acid orfatty acid ester can be obtained by urea fractionation, liquid/liquidpartition chromatography, column chromatography or the like in a purityof at least 80%.

More specifically, the extraction purification of fatty acid can becarried out according to a procedure as described in Japanese UnexaminedPatent Publication No. 5-91888.

According to the present invention, not only highly purified fatty acid,but also a mixture of free fatty acids (including free omega 9 seriesunsaturated fatty acids), a mixture of fatty acid esters (includingomega 9 series unsaturated fatty acid esters) or a fat and oil(including omega 9 series unsaturated fatty acids in form of a freefatty acid, mono-, di- or tri-glyceride, phospholipid, glycolipid, oramides) can be used. The fat and oil can be obtained by extracting fromcultured microbial cells of microorganisms capable of producing an omega9 series unsaturated fatty acid according to the above-mentioned method.The mixture of free fatty acids or the mixture of fatty acid esters canbe obtained by isolating from the fat and oil according to theabove-mentioned method.

The present composition for prophylaxis or improvement of medicalsymptoms caused by LTB₄ can be formulated from an omega 9 seriesunsaturated fatty acid and conventionally used carrier, excipient,additive etc., and can be used in oral or parenteral forms in the fieldof medicines, quasi-drug, cosmetics, foods or drinks.

The medical symptoms caused by LTB₄, to which the present invention isapplied are, for example, inflammatory symptoms such as erythema andedema, hyperalgesia, ache, inflammatory symptoms resulting from alergicreaction, rheumatoid arthritis, chronic arthritic rheumatics, gout,psoriasis, infections, inflammatory bowel diseases, infusion damage,chronic long diseases, various arthritic symptoms, inflammatory symptomsaccompanying asthma (for example, late stage hypersensitivity), collagendisease, allergic rhinitis, bronchial asthma, atopic dermatitis,tympanitis, urticaria, contact dermatitis, drug allergy, food allergy,insect allergy, arrhythmia, acute myocardial infraction,ischemia-reperfusion damage. Since the present fatty acids selectivelyinhibit the production of LTB₄, side effects are relatively small, andthe fatty acids can be applied to chronic symptoms, and are useful forimprovement of rheumatoid arthritis. In the present invention, thephrase "improvement of symptoms" is used in the broad sense, andincludes treatment of a patient.

Where the present fatty acids are used in a pharmaceutical composition,they can be used in any formulations suitable for oral or parenteraladministration, for example, injections, infusion, powders, granules,tablets, capsules, enteric coated tablets, enteric capsules, troche,mixture for internal use, suspension, emulsion, syrup, liquid forexternal use fomentations, nasal drops, ear drops, eye drops, inhalant,ointment, lotion, suppository etc. They may be used alone or incombination according to the symptom. These formulation may be preparedusing a main component and conventional aids such as excipient, binder,disintegrator, lubricant, corrigent, and the like according to thepurpose. An administration dose varies depending on the purpose of theadministrations and conditions of a subject which receives thecomposition such as sex, age, weight etc., and usually, where the fattyacid is orally administered to an adult human, its daily does is 1 to1000 mg, and preferably 1 to 500 mg, and more preferably 1 to 200 mg;and for parenteral administration, daily dose is 0.1 to 100 mg, andpreferably 0.1 to 50 mg, and more preferably 0.1 to 20 mg.

It is known that fatty acids as active ingredients of the presentinvention are biosynthesized in-vivo under an essential fatty aciddeficient condition. In addition, when the present fatty acids werecontinuously orally administered to IRC male mice of 7 weeks old at adose of 2 g/day/kg for 2 weeks, abnormal symptom was not observed.Therefore, the present fatty acids are excellent in a safety point ofview.

In the case where the present fatty acids are used in a form of foods ordrinks, the fatty acids may be not only in a form of the above-mentionedformulation, but also may be added to a food stuff, especially, to afood stuff not containing the present omega 9-series unsaturated fattyacid, and a food may be manufactured according to a conventionalprocedure. The amount of fatty acids to be added to a food stuff variesdepending on the nature of food, and preferably 0.001 to 50% relating tothe total weight of the food, though it is not limited to this range.

Healthy foods or functional foods containing the present fatty acid areused for prevention or improvement of medical symptoms caused by LTB₄.The forms thereof may be not only the above-mentioned pharmaceuticalformulations, but also may be processed foods such as liquid food,semi-digested nutrient food, component nutrient food, drinksincorporating, in addition to the present fatty acids, for exampleproteins, sugars, fats, minor elements, vitamins, emulsifier, perfumeetc. As the above-mentioned proteins, are used milk protein, soybeanprotein, egg albumin, which have high nutrient value with good aminoacid balance. In addition functional food in-situ prepared by adding thepresent fatty acid to a food may be provided to patients, in a hospitalunder control by a dietician according to a nutritional prescriptionprescribed by a doctor.

Foods containing the present fatty acid are preferably orally taken toan adult human in an amount which provides 1 to 1000 mg/day, andpreferably 1 to 500 mg/day, and more preferably 1 to 200 mg/day of thefatty acid, for the purposes of prevention or improvement of medicalsymptoms caused by LTB₄, or for maintaining healthy condition.

The foods or drinks containing the present fatty acid may be foods orgrocery items in a form of solid or liquid, for example, bread, noodle,rice, confectioneries such as biscuit, cake, candy, chocolate, Japanesesweets, agricultural food products such as soybean curd and derivativesthereof, fermentation products such as Japanese sake or medicalbeverage, sweet sake, vinegar, soy sauce, dressings, stock farm productssuch as yogurt, ham, bacon, sausage or mayonnaise, fish product such asboiled fish paste or fried fish paste, drinks such as juice, refreshingdrink, sports drink, alcoholic drink, tea, and the like.

EXAMPLES

Now, the present invention is more specifically explained by Examples.

Example 1

To 10 g of an omega 9 series unsaturated fatty acid-containingtriglyceride (containing 12.45% 6,9-cis-octadecadienoic acid, 3.65%8.11-cis-eicosadienoic acid, and 14.44% 5,8,11-cis-eicosatrienoic acid)and 1.2 g of yolk phospholipid, was added 2.5% aqueous glycerol solutionto make the total weight 100 g to prepare an emulsion. 5 rabbits(weighing 3.5 Kg) were injected with 30 ml of the emulsion through atail vein, and before the injection (0 hour) and 6 hours from theinjection, blood samples were obtained. The blood sample was mixed withthe same volume of PBS, and polymorphonuclear leukocyte (PMNL) wasobtained by a Ficoll-Conray overlay method. To the PMNL was addedcalcium ionophore A23187 to the concentration of 1 μg/ml, and LTB₄produced was measured by reversed phase high performance liquidchromatography. The result is shown in Table 1.

                  TABLE 1                                                         ______________________________________                                        Amount of LTB.sub.4 produced (ng/10.sup.7 PMNL)                               Before injection                                                                            6 hours after injection                                         ______________________________________                                        16.9          8.1                                                             20.8          9.5                                                             24.4          19.3                                                            14 5          2.4                                                             15.9          1.5                                                             18.50 ± 4.05.sup.(1)                                                                     8.15 ± 7.14.sup.(2)                                          ______________________________________                                         .sup.(1) Mean ± Standard deviation                                         .sup.(2) P < 0.05                                                        

Example 2

10 g of 6,9-cis-octadecadienoic acid ethyl ester (95% purity) or 10 g of8,11-cis-eicosadienoic acid ethyl ester (95% purity) or 10 g of5,8,10-cis-eicosatrienoic acid ethyl ester (95% purity), and 1.2 g ofyolk phospholipid were mixed, and 2.5% aqueous glycerol solution wasadded thereon to make the total weight 100 g, to prepare emulsion A,emulsion B or emulsion C, respectively. 3 ml of the emulsion A, B or Cwas injected to 5 rabbit (weighing 3.5 kg) through a tail vein, andbefore the injection (0 hour) and 6 hours from the injection, an amountof LTB₄ produced by polymorphonuclear leukocyte (PMNL) was measuredaccording to the same procedure as described in Example 1. The result isshown in Table 2.

                  TABLE 2                                                         ______________________________________                                        Amount of LTB.sub.4 produced (ng/10.sup.7 PMNL)                               Emulsion   Before injection                                                                            6 hours after injection                              ______________________________________                                        A          18.96 ± 3.89                                                                             13.06 ± 2.91*                                     B          18.30 ± 3.56                                                                             9.88 ± 2.33**                                     C          20.36 ± 3.45                                                                             6.86 ± 3.31**                                     ______________________________________                                         Mean ± Standard deviation                                                  *P < 0.05                                                                     **P < 0.01                                                               

As can be seen from the above, the emulsions A, B and C significantlyinhibited the production of LTB₄, and especially inhibitory action ofthe emulsion C(containing 5,8,11-cis-eicosatrienoic acid ethyl ester) isexcellent.

Example 3

Male Wister rats, 5 weeks old, were divided into two groups eachconsisting of 6 rats. The first group received a feed composed of 90% oflipid-free powder diet, 8% of lard and 2% of omega 9 series unsaturatedfatty acid-containing triglyceride (containing 19.99%6,9-cis-octadecadienoic acid, 2.00% 8,11-cis-eicosadienoic acid and18.62% 5,8,11-cis-eicosatrienoic acid). Another group received a feedcomposed of 90% of lipid-free powder diet, 8% of lard and 2% of soybeanoil. After 15 days, 0.1 ml of a saline containing 1% (W/N) carrageenin(Type IV, Sigma Chemical Co., St. Louis, Mo.) was injected into theright hind foot pad of each rat, and 4 hours later a swelling ratio wascalculated from a measurement of the footpad volume according to thefollowing equation. ##EQU1##

Swelling ratio for the group which received omega 9 series fattyacid-containing triglyceride was 44.6±4.3%, while that for the groupwhich received soybean oil was 61.0±11.3%. Therefore, the swelling ratiowas significantly reduced (P<0.05) by administration of omega 9 seriesunsaturated fatty acids.

Example 4

180 mg of 5,8,11-cis-eicosatrienoic acid ethyl ester was filled into asoft capsule shell composed of the following components:

Gelatin 70.0%

Glycerine 22.9%

Methyl paraoxybenzoate 0.15%

Propyl paraoxybenzoate 0.51%

Water valance

Total 100%

to obtain a soft capsule.

Example 5

2 g of β-cyclodextrin was added to 20 ml of 20% ethanol aqueoussolution, and 100 mg of 5,8,11-cis-eicosatrienoic acid ethyl ester wasadded thereon while stirring the mixture with a stirrer, and the mixturewas incubated at 50° C. for 2 hours. After cooling to a room temperature(for about 1 hour), the mixture was further incubated at 4° C. for 10hours while stirring. Resulting precipitate was recovered bycentrifugation, washed with n-hexane, and lyophilized to obtain 1.8 g ofcyclodextrin inclusion compound containing 5,8,11-cis-eicosatrienoicacid ethyl ester. 1 g of this powder was homogeneously mixed with 10liters of juice to prepare 5,8,11-cis-eicosatrienoic acid ethylester-containing juice.

Example 6

An animal test was carried out according to a method of T. S. Courtensy(Nature 283, 666, 1980) with slightly modification. Namely, DBA/lJNCrjmice, 7 week old, weighing 20 g (Charles River Japan Inc.) were used.One group consisted of 10 mice. For antigen preparation, 0.3% bovinetype II collagen (Collagen Gijutsu Kenshukai) was emulsified with aequal volume of Freund's complete adjuvalent (INC Biomedica Inc.) Eachmouse was injected intradermally on the root of tail with 0.1 ml of theantigen preparation. After 14 days from the injection, each mouse wasboosted by intraderml injection with bovine type II collagen (CollagenGijutsu Kenshukai) emulsified with Freund's incomplete adjuvant (DIFCO)at the same volumes to generate arthritis.

The test group orally received 1 mg/kg of a mixture of mead acid(comprising 90.1% and acid ethyl ester 7.9% 6,9-cis-octadecadienoic acidethyl ester, 1.4% oleic acid ethyl ester, 0.6% arachidic acid ethylester) (mixed in olive oil 200 μl per mouse) and the control grouporally received olive oil (200 μl) 5 times per week, starting at theseventh day from the first immunization. The positive control groupreceived auranofin (10 mg/kg, intraperifoneal administration, SmithKline Beecham Seiyaku).

The severity of arthritis was scored as follow (designated as RAscore, 0to 4 point for one paw, at most 16 point in total for four paws).Namely, point 0: no change point 1: weak swelling and weak reddish,point 2: weak swelling and reddish, point 3: strong swelling andreddish, point 4: storing swelling accompanied with deformation of boneand reddish were used as a evaluation standard. As a result,administration of mead acid (1 mg/kg) provided decrease of the RAscore,and arthritis was improved. The decreasing effect was about 30% on the35th day from the second immunization, which was the same as thepositive control group which received auranofin. A result is shown inFIG. 1.

We claim:
 1. A method for the prevention or treatment of allergy causedby leucotriene B4 (LTB4) in a patient in need thereof comprisingadministering to said patient an omega 9 series unsaturated fatty acid,wherein said omega 9 series unsaturated fatty acid is at least one of6,9-octadecadienoic acid, 8,11-eicosadienoic acid or5,8,11-eicosatrienoic acid, in an amount effective for preventing ortreating said allergy.
 2. The method according to claim 1, wherein theomega 9 series unsaturated fatty acid is 6,9-octadecadienoic acid. 3.The method according to claim 1, wherein the omega 9 series unsaturatedfatty acid is 8,11-eicosadienoic acid.
 4. The method according to claim1, wherein the omega 9 series unsaturated fatty acid is5,8,11-eicosatrienoic acid.
 5. The method according to claim 1, wherein6,9-octadecadienoic acid, 8,11-eicosadienoic acid and5,8,11-eicosatrienoic acid are administered.
 6. The method according toclaim 1, wherein the omega 9 series unsaturated fatty acid is orally orparenterally administered.
 7. The method according to claim 6, whereinthe omega 9 series unsaturated fatty acid is orally administered in anamount of between about 1 to 1000 mg per day.
 8. The method according toclaim 7, wherein the omega 9 series unsaturated fatty acid is orallyadministered in an amount of between about 1 to 500 mg per day.
 9. Themethod according to claim 8, wherein the omega 9 series unsaturatedfatty acid is orally administered in an amount of between about 1 to 200mg per day.
 10. The method according to claim 6, wherein the omega 9series unsaturated fatty acid is orally administered in an amount ofbetween about 0.1 to 100 mg per day.
 11. The method according to claim10, wherein the omega 9 series unsaturated fatty acid is orallyadministered in an amount of between about 0.1 to 50 mg per day.
 12. Themethod according to claim 11, wherein the omega 9 series unsaturatedfatty acid is orally administered in an amount of between about 0.1 to20 mg per day.
 13. A method according to claim 1, wherein the allergy isrheumatoid arthritis.
 14. A method for the prevention or treatment ofallergy caused by leucotriene B4 (LTB4) in a patient in need thereofcomprising administering to said patient a food or drink which comprisesan omega 9 series unsaturated fatty acid, wherein said omega 9 seriesunsaturated fatty acid is at least one of 6,9-octadecadienoic acid,8,11-eicosadienoic acid or 5,8,11-eicosatrienoic acid, in an amounteffective for preventing or treating said allergy.
 15. The methodaccording to claim 14, wherein the omega 9 series unsaturated fatty acidis 6,9-octadecadienoic acid.
 16. The method according to claim 14,wherein the omega 9 series unsaturated fatty acid is 8,11-eicosadienoicacid.
 17. The method according to claim 14, wherein the omega 9 seriesunsaturated fatty acid is 5,8,11-eicosatrienoic acid.
 18. The methodaccording to claim 14, wherein 6,9-octadecadienoic acid,8,11-eicosadienoic acid and 5,8,11-eicosatrienoic acid are administered.19. The method according to claim 14, wherein the omega 9 seriesunsaturated fatty acid is present in an amount of from 0.001 to 50% byweight of the total food or drink.
 20. A method according to claim 14,wherein the allergy is rheumatoid arthritis.